Geriatric Sleep Disorder

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Background

Sleep disorders are commonly underdiagnosed and are a significant source of concern in the geriatric population.[1] Several diverse factors may contribute to sleep disturbances in a large percentage of the elderly population. These include retirement, health problems, death of spouse/family members, and changes in circadian rhythm.[2] Changes in sleep patterns may be part of the normal aging process; however, many of these disturbances may be related to pathological processes that are not considered a normal part of aging.[3, 4]

In addition to affecting quality of life—because of excessive daytime sleepiness, as well as physical, psychological, and cognitive problems[4] —sleep disorders have been implicated with increased mortality.[5, 6] In addition, the number of medications used tends to increase with age, which in itself can lead to increased morbidity, mortality, and side effects such as falls,[7] cognitive impairment, and even sleep disturbances.[8]

When a person experiences significant and prolonged sleep disturbance, they will generally contact their primary care provider for an evaluation. This evaluation may consist of a medical history review, concomitant medications, physical examination, lab work, and a Mental Status Examination. If the provider is unable to determine the underlying causality of the sleep disturbance, referral to a psychiatrist or sleep specialist may be necessary. At this point, a more in-depth examination is performed to rule out other potential contributing factors and to reach a diagnosis. Determining the causality of the sleep disturbance is imperative to be able to educate patients and caregivers about treatment alternatives.

Treating insomnia in the elderly can improve overall health, but care must be taken when medications are used in this particular population.[1] Treatments for insomnia include over-the-counter and prescription medications. However, non-medication treatment options are preferred and may lead to more durable benefits. Non-medication treatments include behavioral modification, relaxation techniques, sleep hygiene improvement, sleep restriction, light therapy,[9] cognitive-behavioral therapies,[3, 10] tai chi, yoga, meditation, acupuncture, and acupressure.[11]  There is even an FDA-approved bedside device for insomnia that cools and pumps fluid to a forehead pad that is worn throughout the night. The device helps reduce latency to stage 1 and stage 2 sleep.[12]

Pathophysiology

Normal sleep is organized into different stages that cycle throughout the night. Polysomnographic studies have classified the sleep stages into rapid-eye-movement (REM) sleep and non-REM sleep

REM sleep (ie, paradoxical desynchronized sleep) is the stage of sleep during which muscle tone decreases markedly; this stage is associated with bursts of conjugate gaze and dreaming. Relative amounts of REM sleep are maintained until extreme old age, when they show some decline.

Non-REM sleep is subdivided into 4 stages. Stages 1 and 2 constitute light sleep, and stages 3 and 4 are called deep sleep or slow-wave sleep (SWS). With aging, an increase in the duration of stage 1 sleep and an increase in the number of shifts into stage 1 sleep occur. Stages 3 and 4 decrease markedly with age; in extreme old age (>90 years), stages 3 and 4 may disappear completely. Some studies, however, have found that elderly women tend to have normal or even increased stage 3 sleep, whereas men have normal or reduced stage 3 sleep.

Definitions

Time in bed

Older individuals spend more time lying in bed at night without attempting to sleep or unsuccessfully trying to sleep. They also use the bed for resting and napping during the day.

Total sleep period

Total sleep period refers to the time from sleep onset to the final awakening from the main sleep period of the day. Total sleep period increases with age because of the increase in the number of awakenings.

Total sleep time

Total sleep time refers to the total sleep period minus the time spent awake during the sleep period. Studies have found the total sleep time to be either reduced or unchanged in the older population.

Sleep latency

Sleep latency is the time from the decision to sleep to the onset of sleep. Studies have found considerable variability in individuals. In females, sleep latency has been related to increases in age and hypnotic drug use, which would decrease sleep latency.

Wake after sleep onset

Wake after sleep onset is the time spent awake from sleep onset to final awakening. An increase occurs in the time spent awake after sleep onset in the older population. Webb was able to attribute 38% of nocturnal arousals in a study to physical discomfort (eg, bladder distention, urinary urgency).[13] Pain, restless legs, and dyspnea have also been identified as factors in arousal during sleep.

Sleep efficiency

Sleep efficiency is the ratio of total sleep time to nocturnal time in bed. Most studies have found sleep efficiency to be decreased in the older population.

Nocturnal penile tumescence

Studies have shown that a gradual decline in nocturnal penile tumescence (NPT) during REM sleep occurs with age, even though the duration of REM sleep remains fairly constant until extreme old age.

Other changes

Few data describe cardiovascular changes during sleep in the older population. Zepelin found that auditory awakening thresholds from stage 4 sleep were significantly lower during the first night's sleep in a sleep laboratory in older men than in younger men.[14]

Older people spend more time in bed to get the same amount of sleep they obtained when they were younger; however, the total sleep time, at most, is only slightly decreased, with an increase in nocturnal awakenings and daytime napping. They often report having earlier bedtimes and an increased sleep latency (time to fall asleep), but excessive daytime somnolence is not part of normal aging. Older persons have been observed to be more easily aroused from sleep by auditory stimuli, suggesting increased sensitivity to environmental stimuli.

Etiology

Sleep apnea and periodic limb movements in sleep

Two primary sleep disorders that increase with age are obstructive sleep apnea (OSA) and periodic limb movements in sleep (PLMS).

OSA is the lack of breathing during sleep, and it can be obstructive (upper airway occlusion), central (primary neurologic disease), or mixed. People with OSA may experience waking with gasping, confused wandering in the night, and thrashing during sleep.

Because waking resolves OSA, avoid sedatives and hypnotics in these patients because such agents can further relax the pharynx dilators, thereby worsening the apnea. Martin et al found that among healthy older adults living in community settings, the prevalence of OSA (defined by more than 5 apneas per hour) was 28% in men and 20% in women.[15] They also found that among a random sample of patients in a medical ward, the prevalence of OSA was higher (33%).[15] This may be because of the high incidence of congestive heart failure (CHF) in this group. Significantly, many elderly inpatients are prescribed hypnotics, which can exacerbate OSA. OSA occurs in 42% of people with dementia who live in nursing homes and correlates with cognitive function.

An interaction between OSA and the cognitive deterioration of dementia is likely.[16, 17, 18] Sedative-hypnotic medications will likely exacerbate sleep apnea and are not recommended in patients with OSA. OSA can result in daytime hypersomnolence, systemic hypertension, cardiac arrhythmias, cor pulmonale, and sudden death.

PLMS, or nocturnal myoclonus, is repetitive, unilateral, or bilateral stereotyped leg jerks that arouse the patient from sleep. In a random sample of 427 older volunteers, 45% had PLMS; this statistic correlated with dissatisfaction with sleep, sleeping alone, and kicking at night. The incidence of nocturnal myoclonus increases with age, and the likelihood of an associated sleep-wake complaint is related to the absolute number and intensity of the leg movements.

Sundowning

Sundown syndrome is a behavioral phenomenon closely related to disturbed circadian rhythms[19] with incident rates of up to 66% in patients with dementia and those in nursing homes.[20, 21, 22, 23] Behaviorally, it is characterized by agitation, aggression, confusion, disorientation, and mood disturbances.[22, 24] Its name, “sundowning,” reflects that it is typically observed in the late afternoon or evenings. Sundowning behaviors have been associated with functional impairment, rapid decline of cognition, financial toll, caregiver burden, and increased risk of institutionalization.[23, 25]  

Psychiatric disorders

Psychiatric illnesses such as dementia and depression are often associated with insomnia.[26, 27, 28] Of elderly patients with major depressive disorders, 50% report substantial sleep impairment. Clinical tools such as the Mini–Mental State Examination (MMSE) and/or Geriatric Depression Scale (GDS) should be used. An attempt should be made to manage the underlying condition before initiating treatment for sleep.

A patient who is depressed may experience an increase in sleep latency, a decrease in REM latency, prolonged initial rapid-eye-movement (REM) sleep, an increase in nighttime wakefulness, a decrease in slow-wave sleep (SWS), and early-morning awakening.

Patients with dementia, especially those with Alzheimer disease, have lower sleep efficiency; an increase in the length of stage 1 sleep; a decrease in stage 3, stage 4, and REM sleep; more sleep disruptions and awakenings; episodes of nocturnal wandering; and an increase in daytime napping.[29]

Personality and affective disorders can lead to poor sleep or subjective complaints of poor sleep. This can further manifest as early-morning wakefulness, a reduction of stage 4 sleep, and short REM latency, which is more pronounced in the older population. Bipolar disorders, schizophrenia, posttraumatic stress disorder (PTSD), and anxiety disorders can result in difficulty initiating and/or maintaining sleep.

Medications

Older patients take an average of 5–9 daily medications, some of which can interfere with sleep and wakefulness. Sedative antidepressants (eg, amitriptyline) and sedative neuroleptics (eg, chlorpromazine, clozapine) can cause impaired performance and daytime drowsiness. Avoid amitriptyline in older people because of the anticholinergic effects and possible confusion. Beta-blockers, especially lipophilic compounds (eg, metoprolol, propranolol), can cause difficulty falling asleep, an increased number of awakenings, and vivid dreams.

The chronic use of sedative-hypnotics often confounds normal sleep-wake functioning because of drug-withdrawal effects or daytime drowsiness. The xanthines theophylline and caffeine are stimulants that increase wakefulness while they decrease SWS and total sleep time. The effect of caffeine can last as long as 8-14 hours and may be more pronounced in older patients because of decreased caffeine clearance with decreased liver function. Furthermore, caffeine is present in many over-the-counter medications, including analgesics, cold or allergy remedies, and appetite suppressants.

Nicotine is also a stimulant and affects sleep in a manner similar to that of caffeine. Several studies have shown that people of all ages who smoke have more sleep disturbances than people who do not smoke, primarily difficulty falling asleep and decreased sleep duration.

Other causes

Other causes of sleep disorders in geriatric patients include the following:

Epidemiology

More than 50% of elderly people have insomnia.[30] Sleep disturbance or insomnia is the third most common patient complaint, ranking behind headaches and the common cold. Approximately 15% of the adult population in the United States has insomnia of significant enough severity to seek medical attention. Of the US population, 1.7% receive a hypnotic prescription annually, and another 0.8% purchase nonprescription sleep aids. Fifty million Americans occasionally take some form of sleep medication.

Older women are more likely to experience insomnia than older men. In a large epidemiologic study of people older than 70 years, 35% of women reported moderate to severe insomnia, compared to only 13% of men.[31] More than one half of people older than 64 years who live at home and two thirds of people older than 64 years who reside in a long-term care facility are estimated to have some form of sleep disturbance.

Prognosis

In addition to affecting quality of life, sleep disorders have been associated with increased mortality. Two primary sleep disorders that increase with age are obstructive sleep apnea (OSA) and periodic limb movements in sleep (PLMS). OSA can result in daytime hypersomnolence, systemic hypertension, cardiac arrhythmias, cor pulmonale, and sudden death. In a random sample of 427 older volunteers, 45% had PLMS, and they reported dissatisfaction with sleep, sleeping alone, and kicking at night. Yaffe et al suggested that older women with sleep-disordered breathing (SDB), characterized by recurrent arousals from sleep and intermittent hypoxemia, have an increased risk of developing cognitive impairment.[32]

In a study of SDB and nocturnal cardiac arrhythmias in older men, Mehra et al found that the likelihood of atrial fibrillation or complex ventricular ectopy (CVE) increased along with the severity of SDB. In addition, different forms of SDB were associated with the different types of arrhythmias.[33]

Polysomnography in 2,911 participants showed that the odds of atrial fibrillation and of complex ventricular ectopy increased with increasing quartiles of the respiratory disturbance index (a major index including all apneas and hypopneas). Central sleep apnea was more strongly associated with atrial fibrillation than with complex ventricular ectopy. In contrast, obstructive sleep apnea and hypoxia were associated with complex ventricular ectopy; participants in the highest hypoxia category had an increased odds of CVE compared with those in the lowest quartile. The results suggest that different sleep-related stresses may contribute to atrial and ventricular arrhythmogenesis in older men.[33]

Patient Education

Individuals should be made aware that obtaining 8 hours of sleep per night is not crucial. Sleep needs are individualized. Although one person may need 9 hours of sleep, another person may need only 5 hours. Also, the amount of sleep required may change with age. If a significant change in amount of sleep occurs but there are no disturbances in daily functioning, there shouldn't be a cause for worry. When significant disturbances in daily functioning have occurred, it is important to identify the cause of the sleep disturbance and discuss available treatment options.

A variety of treatment options are available for insomnia and do not necessarily include the use of prescription medications. However, if prescription medications are warranted, there are many to choose from. Certain medications should be avoided in the elderly population (see Medication).

Experts suggest stimulus control,[34] which means using the bed for only sleep and sex. If people are used to reading or watching television in bed, they are encouraged to leave the bedroom and engage in a relaxing activity elsewhere until they are sleepy and ready to return to bed.

Teaching patients muscle-relaxation techniques to reduce tension and promote sleep is also useful. Regardless of the underlying causes of insomnia, general habits should be practiced for good sleep.

Patients should be instructed to go to bed at the same time, wake up at the same time, and avoid daytime napping, caffeine, heavy meals, nicotine, alcohol, and exercise at bedtime. Sedentary elderly persons should be encouraged to start a daily exercise program in the morning, as moderate training (60 min/d) has been shown to improve sleep quality.[35] Another useful tool is to turn the bedroom into an environment that is quiet, dark, and cool and ultimately promotes sleep.

The Web sites below provide further education on insomnia. These sites have information on signs and symptoms, causality, preventive measures, complications, treatments, and even current enrollment in clinical trials for insomnia.

History

Evaluation of sleep disorder in elderly patients begins with a complete sleep history. The assessment of includes a detailed multidisciplinary approach. Sleep-related problems in the elderly include hypersomnia, disorientation, delirium, impaired intellect, decreased cognition, psychomotor complaints, increased accidents, and falls.[36] In the geriatric population, the most frequent complaints are problems initiating or maintaining sleep.[37]

Whenever possible, interview the bed partner, because he or she often notices problems with the patient's sleep of which the patient is unaware.

A good sleep history includes questions relating to typical sleep at night; daytime functioning; presence of medical conditions; intake of caffeine, alcohol, drugs, or food before bedtime; and the history of psychiatric and mood disorders.

The following questions may also be considered:

These data help determine the sleep pattern of the patient, the severity of the disorder, and the possible causes leading to sleep disturbances. They also help differentiate between SA and PLMS.

Having the patient maintain a sleep diary for several weeks before arriving for assessment is advisable. This provides a reliable perspective about the patient's condition for the clinician, and the patient learns more about his or her sleeping patterns.

Remember that individuals with this disorder have a lifetime risk for suicide, which is significant. Inquiring about suicidal ideation at each visit is always important. In addition, the interviewer should inquire about past acts of self-harm or violence.

Ask the following types of questions when determining suicidal ideation or intent:

If the reply is positive for these thoughts, inquire about specific plans, suicide notes, family history (anniversary reaction), impulse control and access to firearms. If the patients has suicidal thoughts, the chart should document that the patient does not have an immediate plan or that he/she was referred for psychiatric hospitalization.[38]

Inquiring about homicidal ideation or intent during each patient interview is also important. Ask the following types of questions to help determine homicidal ideation or intent:

If the reply to one of these questions is positive, ask the patient if he or she has any specific plans to injure someone and how he or she plans to control these feelings if they occur again.

If the patient has homicidal ideation, refer the patient immediately for psychiatric hospitalization.

Physical Examination

Physical examination and the Mental Status Examination may give clues to the causes of sleep disturbance (eg, obesity with resulting obstructive sleep apnea [SA], depression). In addition, potential complications of sleep disorders, such as hypertension from obstructive SA, may also be discovered.

Obtain a complete medical history, and perform a complete Mental Status Examination, physical examination, and neurologic examination to assist with the evaluation and rule out other disease processes.

Because of the variability of the presentation of the disorder, any or all symptoms of insomnia or other sleep disorders may manifest, depending on the presenting subtype. Examples of items to assess in the Mental Status Examination are listed below.

Approach Considerations

After a detailed history, a clinician may find it necessary to refer the patient to a sleep disorders center for evaluation of sleep apnea. A full-night polysomnogram records brain waves by electroencephalography (EEG); eye movement by electro-oculography (EOG); chin muscle tension and leg movements by electromyography (EMG); heart rate by electrocardiography (ECG); and blood oxygen saturation levels by pulse oximetry.

Portable recorders are also used as screening tools. These devices are placed on patients in the afternoon, and patients are then sent home to sleep on their beds at night. These systems are more convenient and less expensive than a laboratory polysomnogram.

Ferritin levels of less than 50 ng/mL have been found to be present in elderly patients with restless legs syndrome.

Approach Considerations

The geriatric population is the largest group of people who use hypnotic drugs. People older than 60 years receive 33% of all hypnotic prescriptions, although they constitute only 14% of the population. The use of sedative-hypnotics by the elderly population has been associated with falls, hip fractures, and daytime carryover symptoms. When evaluating a patient, exclude primary sleep disorders and review medications and other contributory medical conditions.

Patient education on age-related changes in sleep and good sleep hygiene may be adequate treatment for many older adults. If the initial history and physical examination findings do not reveal a serious underlying cause, a trial of improved sleep hygiene is the best initial approach.

The common recommended measures include the following:

People who are overweight and habitually snore loudly may be helped by weight loss. All people who snore loudly should abstain from alcohol or other sedatives before going to bed. They should also take measures to avoid supine sleeping (eg, by taping a tennis ball to the back of their bedclothes).

In the absence of obstructive sleep apnea (OSA), contributing conditions, such as allergies, nasal pathology, or nasopharyngeal enlargement, should be sought and adequately managed by intranasal corticoid sprays or evaluated by an ear, nose, and throat specialist. If the sleep problem is secondary to a medical problem, treat the primary problem rather than the sleep problem. Polysomnography is indicated when primary sleep disorders such as SA or periodic limb movements in sleep (PLMS) are suspected.

Consultation with appropriate specialists may be indicated, depending on the underlying causes of the sleep disorder, such as psychiatric consultation for severe depression and pulmonary or surgical consultation for obstructive sleep apnea. Psychologists may provide cognitive-behavioral therapy for insomnia.

For older patients who are computer savvy, computerized cognitive-behavioral therapy for insomnia (CCBT-I) may be a more attractive approach than the traditional face-to-face therapy sessions. In a meta-analysis, CCBT-I using Internet programs improved several sleep parameters and showed a high treatment adherence rate.[39]

Medication Summary

Before any medications are prescribed, the first priority should be to determine the underlying cause of the sleep disorder, rather than just treat insomnia symptomatically. Usually, treatment on a short-term basis together with sleep hygiene is appropriate for transient insomnia, such as insomnia secondary to bereavement or acute hospitalization. Medications used for insomnia in this population include antidepressants, nonbenzodiazepines, a melatonin agonist, and herbals. Medications, if used, should be started with a low dose and monitored for side effects.[40]

There are several medications used in the treatment of sundowning including melatonin, antipsychotics, antidepressants, benzodiazepines, and cannabinoids. While commonly used, there is little evidence to suggest benefits associated with the use of benzodiazepines and cannabinoids, and due to the significant negative side effects associated, the use of these agents should be avoided.[41, 42] Antipsychotics are commonly used and are recommended as possible treatments in national guidelines, yet there are only limited data that show minimal benefits for these patients.[43, 44] There have been few double-blind, randomized controlled trials evaluating the use of exogenous melatonin.[45] Overall, these studies show some behavioral improvement with extended use.[46] Melatonin dosage widely varied in these studies between 1.5 mg and 10 mg. Several non-pharmacological strategies have been used and have shown to have some beneficial impact on circadian rhythm and possibly nighttime behavioral disturbances in patients with dementia including physical exercise,[47, 48] aromatherapy,[49] music therapy,[50] and bright light therapy.[51] Three treatment principles are suggested when considering treatments for sundown syndrome: (1) the treatment process is a trial-and-error approach, (2) start with lower dosages and slowly titrate upwards, and (3) multi-component therapy (non-pharmacological and pharmacological) may be indicated.[52] Further investigation of non-pharmacological and pharmacological-targeted strategies would be of benefit.[53]

Zolpidem (Ambien, Edluar, ZolpiMist)

Clinical Context:  Zolpidem is structurally dissimilar to benzodiazepines but similar in activity, with the exception of having reduced effects on skeletal muscle and seizure threshold. At recommended doses, it is as effective as triazolam. Adverse CNS effects (eg, nightmares, agitation, drowsiness) have been noted in 10% of patients. In May 2013 the FDA warned that patients taking zolpidem extended release (6.25 mg or 12.5 mg) should not drive or engage in other activities that require full alertness the day after taking the drug. As with benzodiazepine hypnotics, zolpidem is approved only for short-term use (maximum, 3-4 weeks); if used longer, they should be used for only 2-3 nights per week and for no more than 3 months.

According to the 2012 AGS Beers Criteria zolpidem should be avoided in patients with dementia and cognitive impairment because of adverse CNS effects.

Zaleplon (Sonata)

Clinical Context:  Zaleplon is a short-acting pyrazolopyrimidine hypnotic with full agonistic activity on central benzodiazepine receptors (B21 type). It has a short half life (1 hour) and at small doses, it is an effective sleep inducer. It is approved only for short-term use (maximum, 3-4 weeks); if used longer, it should be limited to only 2-3 nights per week and for no more than 3 months.

Eszopiclone (Lunesta)

Clinical Context:  Eszopiclone is a nonbenzodiazepine hypnotic pyrrolopyrazine derivative of the cyclopyrrolone class. The precise mechanism of action is unknown but is believed to be an interaction with the GABA-receptor at binding domains close to or allosterically coupled to benzodiazepine receptors. It is indicated for insomnia to decrease sleep latency and improve sleep maintenance. Eszopiclone has a short half-life, of 6 hours. Higher doses (ie, 2 mg for elderly adults and up to 3 mg for nonelderly adults) are more effective for sleep maintenance, whereas lower doses (ie, 1 mg) are suitable for difficulty in falling asleep.

Class Summary

Barbiturates are not indicated for insomnia, and psychiatric consultation may become necessary for patients receiving barbiturates for many years. Barbiturates are effective only for short-term use, losing much of their effectiveness after 2 weeks of administration. According to the American Geriatrics Society (AGS) 2012 Updated Beers Criteria for Potentially Inappropriate Medications Use in Older Adults, barbiturates should be avoided because of the high risk of overdose, even at low dosages, and of physical dependence.[54] Chloral hydrate should also be avoided in older adults because of tolerance within just 10 days of treatment and risk of overdose with doses just 3 times the therapeutic dose.

Benzodiazepines remain the most commonly prescribed agents for sleep, although users of benzodiazepines tend to report poorer quality of sleep than nonusers.[55, 56] According to the 2012 AGS Beers criteria,[54] all benzodiazepines (short-, intermediate-, and long-acting) should not be used for insomnia in older adults. They can increase the risk of cognitive and psychomotor impairments, falls, fractures, and motor vehicle accidents. Use of benzodiazepines in older adults should be limited to other specific indications such as seizure disorders, REM sleep disorders, benzodiazepine or alcohol withdrawal, severe generalized anxiety disorder, periprocedural anesthesia, and end-of-life care. In 2006 Medicare part D excluded benzodiazepines from drug coverage.

The newer nonbenzodiazepine hypnotics zolpidem, zaleplon, and eszopiclone do not cause rebound insomnia or withdrawal symptoms at discontinuation but can have adverse effects similar to benzodiazepines (delirium, falls, and fractures). In a recent case-cross over study of nursing home residents the nonbenozdiazepine hypnotics were associated with increased risk of hip fracture (OR 1.66) and the risk was even higher for new user (OR 2.20) and residents with cognitive impairment (OR 1.86).[57] These hypnotics should we used with caution in older adults and for no longer than 90 days,[54] even if eszopiclone is approved for prolonged use.

Particular caution should be used in patient with dementia, according to a Cochrane systematic review, there is a lack of randomized controlled trials of benoziazepine or non-benzodiazepine hypnotics in patient with Alzheimer's dementia (AD). Studies of melatonin, either immediate- or slow-realese, did not show an improvement of sleep parameters in patients with AD while a small randomized trial of trazodone 50 mg qHS for two weeks improved nocturnal total sleep time and sleep efficency without serious side effects.[58]

Doxepin (Silenor)

Clinical Context:  Doxepin at low doses (1, 3, and 6 mg) is a selective histamine antagonist (primarily H1 receptor) and is FDA approved for insomnia. Recent studies have shown that low-dose doxepin improves sleep parameters in older adults with a safety profile comparable to placebo.[25, 26] Higher doses of doxepin should be avoided in older adults because of high anticholinergic side effects.[22] Avoid in patients with glaucoma or urinary retention.

Mirtazapine (Remeron)

Clinical Context:  Mirtazapine exhibits both noradrenergic and serotonergic activity. In cases of depression associated with severe insomnia and anxiety, mirtazapine has been shown to be superior to other SSRIs.

Trazodone (Oleptro)

Clinical Context:  Trazodone is an antagonist at the 5-HT2 receptor and minimally inhibits the reuptake of 5-HT. It has negligible affinity for cholinergic and histaminergic receptors. Trazodone is not associated with tolerance or withdrawal effects but it may prolong the QTc interval. Associated orthostatic hypotension can be minimized by administration with food. Limited data exist regarding efficacy in patients who are not depressed, and the FDA has not approved trazodone as a hypnotic.

Class Summary

Sedating antidepressants like trazodone and mirtazapine in low doses are often prescribed at bedtime for insomnia. Little scientific evidence supports efficacy in the treatment of insomnia without associated depression; their use in patients with insomnia without depression is not FDA approved and should be considered off-label use. Doxepin is the only antidepressant, which, at a very low dose, is FDA approved for insomnia.

Ramelteon (Rozerem)

Clinical Context:  Ramelteon is a melatonin receptor agonist with high selectivity for human melatonin MT1 and MT2 receptors. MT1 and MT2 are thought to promote sleep and be involved in maintaining circadian rhythm and a normal sleep-wake cycle. Ramelteon does not cause rebound insomnia or withdrawal symptoms at discontinuation. It is approved for prolonged use. It is indicated for insomnia characterized by difficulty with sleep onset.

Class Summary

Melatonin agonists may promote sleep.

Suvorexant (Belsomra)

Clinical Context:  Suvorexant is an orexin receptor antagonist. The orexin neuropeptide signaling system is a central promoter of wakefulness. Blocking the binding of wake-promoting neuropeptides orexin A and orexin B to receptors OX1R and OX2R by suvorexant is thought to suppress wake drive. It is indicated for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance.

Class Summary

Orexin promotes wakefulness. Antagonism of the orexin receptor suppresses this action by orexin.

Author

Glen L Xiong, MD, Associate Clinical Professor, Department of Psychiatry and Behavioral Sciences, Department of Internal Medicine, University of California, Davis, School of Medicine; Medical Director, Sacramento County Mental Health Treatment Center

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Doctor On Demand<br/>Received income in an amount equal to or greater than $250 from: Blue Cross Blue Shield Federal Employee Program<br/>Received royalty from Lippincott Williams & Wilkins for book editor; Received grant/research funds from National Alliance for Research in Schizophrenia and Depression for independent contractor; Received consulting fee from Blue Cross Blue Shield Association for consulting. for: Received book royalty from American Psychiatric Publishing Inc.

Coauthor(s)

Ariel B Neikrug, PhD, Assistant Professor, Department of Psychiatry and Human Behavior, Director, Behavioral Sleep Medicine Program, University of California, Irvine

Disclosure: Nothing to disclose.

Olivia Vukcevich, BS, Junior Specialist,Department of Psychiatry and Behavioral Sciences, UC Davis Medical Center

Disclosure: Nothing to disclose.

Chief Editor

Ana Hategan, MD, FRCPC, Associate Clinical Professor, Department of Psychiatry and Behavioral Neurosciences, Division of Geriatric Psychiatry, McMaster University School of Medicine; Geriatric Psychiatrist, St Joseph's Health Care Hamilton, Canada

Disclosure: Book royalties and/or honoraria for articles from American Psychiatric Publishing, Springer, and Current Psychiatry.

Additional Contributors

Angela Gentili, MD, Director of Geriatric Medicine Fellowship Program, Professor of Internal Medicine, Division of Geriatric Medicine, Virginia Commonwealth University Health System and McGuire Veterans Affairs Medical Center, Richmond, VA

Disclosure: Nothing to disclose.

Guy E Brannon, MD, Associate Clinical Professor of Psychiatry, Louisiana State University Health Sciences Center; Director, Adult Psychiatry Unit, Chemical Dependency Unit, Clinical Research, Brentwood Behavior Health Company

Disclosure: Received income in an amount equal to or greater than $250 from: Sunovion; Forest.

Acknowledgements

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

References

  1. Subramanian S, Surani S. Sleep disorders in the elderly. Geriatrics. Dec 2007. 62(12):10-32.
  2. Avidan AY. Sleep in the geriatric patient population. Semin Neurol. Mar 2005. 25(1):52-63.
  3. Mahowald MW, Bornemann MA. Sleep Complaints in the geriatric patient. Minn Med. Oct 2007. 90(10):45-7.
  4. Cole C, Richards K. Sleep disruption in older adults. Harmful and by no means inevitable, it should br assessed for and treated. Am J Nurs. May 2007. 107(5):40-9.
  5. Fu Y, Xia Y, Yi H, Xu H, Guan J, Yin S. Meta-analysis of all-cause and cardiovascular mortality in obstructive sleep apnea with or without continuous positive airway pressure treatment. Sleep Breath. 2016 Aug 8. [View Abstract]
  6. Lee WJ, Peng LN, Liang CK, Chiou ST, Chen LK. Long sleep duration, independent of frailty and chronic Inflammation, was associated with higher mortality: A national population-based study. Geriatr Gerontol Int. 2016 Sep 29. [View Abstract]
  7. Latimer Hill E, Cummings RG, Lewis R, Carrington S, Le Couteur DG. Sleep disturbance and falls in older people. J Ger A bio Sci Med. Jan 2007. 62(1):62-6.
  8. Barry PJ, Gallagher P, Ryan C. Inappropriate prescribing in geriatric patient. Curr Psychiatry Rep. Feb 2008. 10(1):37-43.
  9. Gammack JK. Light therapy for insomnia in older adults. Clin Geritr Med. Feb 2008. 24(1):139-49.
  10. Rybarczyk B, Lopez M, Benson R, Alsten C, Stepanski E. Efficacy of two behavioral treatment progrmas for comorbid geriatric insomnia. Psychol Aging. Jun 2002. 17(2):288-98.
  11. Gooneratne NS. Complementary and alternative medicine for sleep disturbance in older adults. Clin Geriatr Med. Feb 2008. 24(1):121-38.
  12. Anderson, P. FDA Approves New Device for Insomnia. Medscape Medical News. Available at http://www.medscape.com/viewarticle/864509. June 8, 2016; Accessed: June 9, 2016.
  13. Webb WB. Age-related changes in sleep. Clin Geriatr Med. 1989 May. 5(2):275-87. [View Abstract]
  14. Zepelin H, McDonald CS. Age differences in autonomic variables during sleep. J Gerontol. 1987 Mar. 42(2):142-6. [View Abstract]
  15. Martin J, Shochat T, Ancoli-Israel S. Assessment and treatment of sleep disturbances in older adults. Clin Psychol Rev. 2000 Aug. 20(6):783-805. [View Abstract]
  16. Buratti L, Luzzi S, Petrelli C, Baldinelli S, Viticchi G, Provinciali L, et al. Obstructive Sleep Apnea Syndrome: An Emerging Risk Factor for Dementia. CNS Neurol Disord Drug Targets. 2016. 15 (6):678-82. [View Abstract]
  17. Sleep apnea increases dementia risk in older women. Harv Womens Health Watch. 2011 Nov. 19 (3):7. [View Abstract]
  18. Buratti L, Luzzi S, Petrelli C, Baldinelli S, Viticchi G, Provinciali L, et al. Obstructive Sleep Apnea Syndrome: An Emerging Risk Factor for Dementia. CNS Neurol Disord Drug Targets. 2016. 15 (6):678-82. [View Abstract]
  19. Martin J, Marler M, Shochat T, Ancoli-Israel S. Circadian rhythms of agitation in institutionalized patients with Alzheimer's disease. Chronobiol Int. 2000 May. 17 (3):405-18. [View Abstract]
  20. Gehrman PR, Martin JL, Shochat T, Nolan S, Corey-Bloom J, Ancoli-Israel S. Sleep-disordered breathing and agitation in institutionalized adults with Alzheimer disease. Am J Geriatr Psychiatry. 2003 Jul-Aug. 11 (4):426-33. [View Abstract]
  21. Evans LK. Sundown syndrome in institutionalized elderly. J Am Geriatr Soc. 1987 Feb. 35 (2):101-8. [View Abstract]
  22. Vitiello MV, Bliwise DL, Prinz PN. Sleep in Alzheimer's disease and the sundown syndrome. Neurology. 1992 Jul. 42 (7 Suppl 6):83-93; discussion 93-4. [View Abstract]
  23. Gallagher-Thompson D, Brooks JO 3rd, Bliwise D, Leader J, Yesavage JA. The relations among caregiver stress, "sundowning" symptoms, and cognitive decline in Alzheimer's disease. J Am Geriatr Soc. 1992 Aug. 40 (8):807-10. [View Abstract]
  24. Bliwise DL. What is sundowning?. J Am Geriatr Soc. 1994 Sep. 42 (9):1009-11. [View Abstract]
  25. Scarmeas N, Brandt J, Blacker D, Albert M, Hadjigeorgiou G, Dubois B, et al. Disruptive behavior as a predictor in Alzheimer disease. Arch Neurol. 2007 Dec. 64 (12):1755-61. [View Abstract]
  26. Wong MM, Brower KJ, Craun EA. Insomnia symptoms and suicidality in the National Comorbidity Survey - Adolescent Supplement. J Psychiatr Res. 2016 Oct. 81:1-8. [View Abstract]
  27. Ohayon MM, Roth T. Place of chronic insomnia in the course of depressive and anxiety disorders. J Psychiatr Res. 2003 Jan-Feb. 37 (1):9-15. [View Abstract]
  28. Chemerinski E, Ho BC, Flaum M, Arndt S, Fleming F, Andreasen NC. Insomnia as a predictor for symptom worsening following antipsychotic withdrawal in schizophrenia. Compr Psychiatry. 2002 Sep-Oct. 43 (5):393-6. [View Abstract]
  29. Bubu OM, Brannick M, Mortimer J, Umasabor-Bubu O, Sebastião YV, Wen Y, et al. Sleep, Cognitive impairment and Alzheimer's disease: A systematic review and meta-analysis. Sleep. 2016 Sep 26. [View Abstract]
  30. Kamel NS, Gammack JK. Insomnia in the elderly: cause, approach, and treatment. Am J Med. Jun 2006. 119(6):463-9.
  31. Byles JE, Mishra GD, Harris MA. The experience of insomnia among older women. Sleep. Aug 2005. 1:28(8):972-9.
  32. Yaffe K, Laffan AM, Harrison SL, et al. Sleep-disordered breathing, hypoxia, and risk of mild cognitive impairment and dementia in older women. JAMA. 2011 Aug 10. 306(6):613-9. [View Abstract]
  33. Mehra R, Stone KL, Varosy PD, Hoffman AR, Marcus GM, Blackwell T, et al. Nocturnal Arrhythmias across a spectrum of obstructive and central sleep-disordered breathing in older men: outcomes of sleep disorders in older men (MrOS sleep) study. Arch Intern Med. 2009 Jun 22. 169(12):1147-55. [View Abstract]
  34. Wu JQ, Appleman ER, Salazar RD, Ong JC. Cognitive Behavioral Therapy for Insomnia Comorbid With Psychiatric and Medical Conditions: A Meta-analysis. JAMA Intern Med. 2015 Sep. 175 (9):1461-72. [View Abstract]
  35. Lira FS, Pimentel GD, Santos RV, et al. Exercise training improves sleep pattern and metabolic profile in elderly people in a time-dependent manner. Lipids Health Dis. 2011 Jul 6. 10:1-6. [View Abstract]
  36. Mirsa S, Malow BA. Evaluation of sleep distubances in older adults. Clin Geriatr Med. Feb 2008. 24(1):15-26.
  37. Ancoli-Israel S, Ayalon. Diagnosis and treatment of sleep disorders in older adults. Am J Geriatr Psychiatry. Feb 2006. 14(2):95-103.
  38. [Guideline] Nakajima GA, Wenger NS. Quality indicators for the care of depression in vulnerable elders. J Am Geriatr Soc. 2007 Oct. 55 Suppl 2:S302-11. [View Abstract]
  39. Cheng SK, Dizon J. Computerised cognitive behavioural therapy for insomnia: a systematic review and meta-analysis. Psychother Psychosom. 2012. 81(4):206-16. [View Abstract]
  40. Tariq SH, Pulisetty S. Pharmacotherapy for insomnia. Clin Geriatr Med. Feb 2008. 24(1):93-105.
  41. Blais J, Zolezzi M, Sadowski CA. Treatment Options for Sundowning in Patients With Dementia. Mental Health Clinician. 2014. 4:189-195.
  42. Kim P, Louis C, Muralee S, Tampi RR. Sundowning syndrome in the older patient. Clinical Geriatrics. April 2005. 13(4):32-36.
  43. American Psychiatric Association. American Psychiatric Association Practice Guidelines for the treatment of psychiatric disorders: compendium 2006. 2006.
  44. Gauthier S, Patterson C, Chertkow H, Gordon M, Herrmann N, Rockwood K, et al. Recommendations of the 4th Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD4). Can Geriatr J. 2012 Dec. 15 (4):120-6. [View Abstract]
  45. de Jonghe A, Korevaar JC, van Munster BC, de Rooij SE. Effectiveness of melatonin treatment on circadian rhythm disturbances in dementia. Are there implications for delirium? A systematic review. Int J Geriatr Psychiatry. 2010 Dec. 25 (12):1201-8. [View Abstract]
  46. Sanchez Z, Bennett L. An integrative research review (IRR) of pharmacological and non-pharmacological interventions of sundowning syndrome in older adults. J Am Geriatr Soc. 2013.
  47. Eggermont LH, Scherder EJ. Ambulatory but sedentary: impact on cognition and the rest-activity rhythm in nursing home residents with dementia. J Gerontol B Psychol Sci Soc Sci. 2008 Sep. 63 (5):P279-87. [View Abstract]
  48. Eggermont LH, Blankevoort CG, Scherder EJ. Walking and night-time restlessness in mild-to-moderate dementia: a randomized controlled trial. Age Ageing. 2010 Nov. 39 (6):746-9. [View Abstract]
  49. Holmes C, Hopkins V, Hensford C, MacLaughlin V, Wilkinson D, Rosenvinge H. Lavender oil as a treatment for agitated behaviour in severe dementia: a placebo controlled study. Int J Geriatr Psychiatry. 2002 Apr. 17 (4):305-8. [View Abstract]
  50. Raglio A, Bellelli G, Traficante D, Gianotti M, Ubezio MC, Villani D, et al. Efficacy of music therapy in the treatment of behavioral and psychiatric symptoms of dementia. Alzheimer Dis Assoc Disord. 2008 Apr-Jun. 22 (2):158-62. [View Abstract]
  51. Forbes D, Culum I, Lischka AR, Morgan DG, Peacock S, Forbes J, et al. Light therapy for managing cognitive, sleep, functional, behavioural, or psychiatric disturbances in dementia. Cochrane Database Syst Rev. 2009 Oct 7. CD003946. [View Abstract]
  52. Boeve BF, Silber MH, Ferman TJ. Current management of sleep disturbances in dementia. Curr Neurol Neurosci Rep. 2002 Mar. 2 (2):169-77. [View Abstract]
  53. Canevelli M, Valletta M, Trebbastoni A, Sarli G, D'Antonio F, Tariciotti L, et al. Sundowning in Dementia: Clinical Relevance, Pathophysiological Determinants, and Therapeutic Approaches. Front Med (Lausanne). 2016. 3:73. [View Abstract]
  54. The American Geriatrics Society 2012 Beers Criteria Update Expert Panel. American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. American Geriatrics Society. Available at http://www.americangeriatrics.org/files/documents/beers/2012BeersCriteria_JAGS.pdf. Accessed: May 21, 2012.
  55. Beland SG, Preville M, Dubois MF, et al. Benzodiazepine use and quality of sleep in the community-dwelling elderly population. Aging Ment Health. 2010 Sep. 14(7):843-50. [View Abstract]
  56. Béland SG, Préville M, Dubois MF, et al. The association between length of benzodiazepine use and sleep quality in older population. Int J Geriatr Psychiatry. 2011 Sep. 26(9):908-15. [View Abstract]
  57. Berry SD, Lee Y, Cai S, Dore DD. Nonbenzodiazepine sleep medication use and hip fractures in nursing home residents. JAMA Intern Med. 2013 May 13. 173(9):754-61. [View Abstract]
  58. McCleery J, Cohen DA, Sharpley AL. Pharmacotherapies for sleep disturbances in Alzheimer's disease. Cochrane Database Syst Rev. 2014 Mar 21. 3:CD009178. [View Abstract]
  59. Lankford A, Rogowski R, Essink B, Ludington E, Heith Durrence H, Roth T. Efficacy and safety of doxepin 6 mg in a four-week outpatient trial of elderly adults with chronic primary insomnia. Sleep Med. 2012 Feb. 13(2):133-8. [View Abstract]
  60. Krystal AD, Durrence HH, Scharf M, Jochelson P, Rogowski R, Ludington E, et al. Efficacy and Safety of Doxepin 1 mg and 3 mg in a 12-week Sleep Laboratory and Outpatient Trial of Elderly Subjects with Chronic Primary Insomnia. Sleep. 2010 Nov. 33(11):1553-61. [View Abstract]
  61. Alessi CA, Yoon EJ, Schnelle JF, et al. A randomized trial of a combined physical activity and environmental intervention in nursing home residents: do sleep and agitation improve?. J Am Geriatr Soc. 1999 Jul. 47(7):784-91. [View Abstract]
  62. Ancoli-Istael S. Sleep disorders in older adults. A primary care guide to assessing 4 common sleep problems in geriatric patients. Geriactrics. Jan 2004. 59(1):37-40.
  63. Avidan AY. Sleep changes and dosorders in the elderly patient. Curr Neurol Neurosci Rep. Mar 2002. 2(2):178-85.
  64. Barthlen GM. Sleep disorders. Obstructive sleep apnea syndrome, restless legs syndrome, and insomnia in geriatric patients. Geriatrics. Nov 2002. 57(11):34-9.
  65. Benca RM. Diagnosis and Treatment of Chronic Insomnia: A Review. Psychiatr Serve. 2005. 56:323-343.
  66. Boot BP, Boeve BF, Roberts RO, Ferman TJ, Geda YE, Pankratz VS. Probable rapid eye movement sleep behavior disorder increases risk for mild cognitive impairment and Parkinson disease: a population-based study. Ann Neurol. 2012 Jan. 71(1):49-56. [View Abstract]
  67. Buysse DJ. Insomnia, Depression, and Aging. Assessing sleep and mood interactions in older adults. Geriatrics. Feb 2004. 59(2):47-51.
  68. Cotroneo A, Gareri P, Lacava R, Cabodi S. Use of zolpidem in over 75-year-old patients with sleep disorders and comorbidities. Arch Gerontol Geriatr Suppl. 2004. 9:93-6.
  69. Edinger JD, Fins AI, Glenn DM, et al. Insomnia and the eye of the beholder: are there clinical markers of objective sleep disturbances among adults with and without insomnia complaints?. J Consult Clin Psychol. 2000 Aug. 68(4):586-93. [View Abstract]
  70. Friedman L, Benson K, Noda A, et al. An actigraphic comparison of sleep restriction and sleep hygiene treatments for insomnia in older adults. J Geriatr Psychiatry Neurol. 2000. 13(1):17-27. [View Abstract]
  71. Gentili A, Edinger JD. Sleep disorders in older people. Aging (Milano). 1999 Jun. 11(3):137-41. [View Abstract]
  72. Gentili A, Weiner DK, Kuchibhatil M, Edinger JD. Factors that disturb sleep in nursing home residents. Aging (Milano). 1997 Jun. 9(3):207-13. [View Abstract]
  73. Jean-Louis G, Kripke DF, Ancoli-Israel S, et al. Sleep duration, illumination, and activity patterns in a population sample: effects of gender and ethnicity. Biol Psychiatry. 2000 May 15. 47(10):921-7. [View Abstract]
  74. Koo BB, Blackwell T, Ancoli-Israel S, Stone KL, Stefanick ML, Redline S. Association of incident cardiovascular disease with periodic limb movements during sleep in older men: outcomes of sleep disorders in older men (MrOS) study. Osteoporotic Fractures in Men (MrOS) Study Group. Circulation. 2011 Sep 13. 124(11):1223-31. [View Abstract]
  75. Kryger M, Monjan A, Bliwise D, Ancoli_Israel S. Sleep, health, and aging. Bridging the gap between science and clinical practice. Geriactrics. Jan 2004. 59(1):24-6,29-30.
  76. Marsh G. Sleep problems in the elderly. Psychiatry Consultation-Liaison Psychiatry and Behavioral Medicine. 1993. 2:1-14.
  77. Mazza M, Della Marca G, De Risio S, Mennuni GF, Mazza S. Sleep disorders in the elderly. Clin Ter. Sep 2004. 155(9):391-4.
  78. O'Keeffe. Secondary causes of restless leg syndrome in older people. Age Ageing. Jul 2005. 34(4):349-52.
  79. Raji MA, Brady SR. Mirtazapine for treatment of depression and comorbidity in alzheimer disease. Ann Pharmacother. Sep 2001. 35(9):1024-7.
  80. Rechtschaffen A, Bergmann BM, Gilliland MA, Bauer K. Effects of method, duration, and sleep stage on rebounds from sleep deprivation in the rat. Sleep. 1999 Feb 1. 22(1):11-31. [View Abstract]
  81. Shimazaki M, Martin JL. Do herbal agents have a place in the treatment of sleep problems in log-term care?. J Am Med Dir Assoc. May 2007. 8(4):248 - 52.
  82. Singh H, becker PM. Novel therapeutic usage of low-dose doxepin hydrochloride. Expert Opin Investig Drugs. aug 2007. 16(8):1295-305.
  83. Vitiello MV. Effective treatments for age-related sleep disturbances. Geriatrics. 1999 Nov. 54(11):47-52; quiz 54. [View Abstract]
  84. Weaver EM, Kapur V, Yueh B. Polysomnography vs self-reported measures in patients with sleep apnea. Arch Otolaryngol Head Neck Surg. 2004 Apr. 130(4):453-8. [View Abstract]
  85. Willcox SM, Himmelstein DU, Woolhandler S. Inappropriate drug prescribing for the community-dwelling elderly. JAMA. 1994 Jul 27. 272(4):292-6. [View Abstract]
  86. Young T, Skatrud J, Peppard PE. Risk factors for obstructive sleep apnea in adults. JAMA. 2004 Apr 28. 291(16):2013-6. [View Abstract]
  87. Youngstedt SD, Kripke DF, Klauber MR, et al. Periodic leg movements during sleep and sleep disturbances in elders. J Gerontol A Biol Sci Med Sci. 1998 Sep. 53(5):M391-4. [View Abstract]
  88. Zepelin H. Sleep disorders. J Gerontol. 1983 May. 38(3):384. [View Abstract]
  89. FDA Drug Safety Communication: FDA warns of next-day impairment with sleep aid Lunesta (eszoplicone) and lowers recommended dose. May 15, 2014. www.fda.gov. Available at http://www.fda.gov/downloads/Drugs/DrugSafety/UCM397277.pdf. Accessed: 6/4/2014.
  90. FDA Drug Safety Communication: FDA approves new label changes and dosing for zolpidem products and a recommendation to avoid driving the day after using Ambien CR. May 14, 2013. www.fda.gov. Available at http://www.fda.gov/Drugs/DrugSafety/ucm352085.htm. Accessed: 6/4/14.